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Myhre syndrome: A first familial recurrence and broadening of the phenotypic spectrum
Author(s) -
Meerschaut Ilse,
Beyens Aude,
Steyaert Wouter,
De Rycke Riet,
Bonte Katrien,
De Backer Tine,
Janssens Sandra,
Panzer Joseph,
Plasschaert Frank,
De Wolf Daniël,
Callewaert Bert
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61377
Subject(s) - short stature , proband , brachydactyly , connective tissue disorder , medicine , genetic disorder , elastin , pathology , mutation , genetics , disease , biology , gene
Myhre syndrome is a rare multisystem connective tissue disorder, characterized by short stature, facial dysmorphology, variable intellectual disability, skeletal abnormalities, arthropathy, cardiopathy, laryngotracheal anomalies, and stiff skin. So far, all molecularly confirmed cases harbored a de novo heterozygous gain‐of‐function mutation in SMAD4 , encoding the SMAD4 transducer protein required for both transforming growth factor‐beta and bone morphogenic proteins signaling. We report on four novel patients (one female proband and her two affected children, and one male proband) with Myhre syndrome harboring the recurrent c.1486C>T (p.Arg496Cys) mutation in SMAD4 . The female proband presented with a congenital heart defect, vertebral anomalies, and facial dysmorphic features. She developed severe tracheal stenosis requiring a total laryngectomy. With assisted reproductive treatment, she gave birth to two affected children. The second proband presented with visual impairment following lensectomy in childhood, short stature, brachydactyly, stiff skin, and decreased peripheral sensitivity. Transmission electron microscopy (TEM) of the dermis shows irregular elastin cores with globular deposits and almost absent surrounding microfibrils and suggests age‐related increased collagen deposition. We report on the first familial case of Myhre syndrome and illustrate the variable clinical spectrum of the disorder. Despite the primarily fibrotic nature of the disease, TEM analysis mainly indicates elastic fiber anomalies.